The University of Southampton
University of Southampton Institutional Repository

Genome-wide association and longitudinal analyses reveal genetic loci linking pubertal height growth, pubertal timing and childhood adiposity

Genome-wide association and longitudinal analyses reveal genetic loci linking pubertal height growth, pubertal timing and childhood adiposity
Genome-wide association and longitudinal analyses reveal genetic loci linking pubertal height growth, pubertal timing and childhood adiposity
The pubertal height growth spurt is a distinctive feature of childhood growth reflecting both the central onset of puberty and local growth factors. Although little is known about the underlying genetics, growth variability during puberty correlates with adult risks for hormone-dependent cancer and adverse cardiometabolic health. The only gene so far associated with pubertal height growth, LIN28B, pleiotropically influences childhood growth, puberty and cancer progression, pointing to shared underlying mechanisms. To discover genetic loci influencing pubertal height and growth and to place them in context of overall growth and maturation, we performed genome-wide association meta-analyses in 18 737 European samples utilizing longitudinally collected height measurements. We found significant associations (P < 1.67 × 10(-8)) at 10 loci, including LIN28B. Five loci associated with pubertal timing, all impacting multiple aspects of growth. In particular, a novel variant correlated with expression of MAPK3, and associated both with increased prepubertal growth and earlier menarche. Another variant near ADCY3-POMC associated with increased body mass index, reduced pubertal growth and earlier puberty. Whereas epidemiological correlations suggest that early puberty marks a pathway from rapid prepubertal growth to reduced final height and adult obesity, our study shows that individual loci associating with pubertal growth have variable longitudinal growth patterns that may differ from epidemiological observations. Overall, this study uncovers part of the complex genetic architecture linking pubertal height growth, the timing of puberty and childhood obesity and provides new information to pinpoint processes linking these traits.
2735-2747
Cousminer, Diana L.
f35f6690-1236-4392-9c4c-867cc437c832
Berry, Diane J.
a624d6c2-49a2-4162-bab2-ed1641c61c51
Timpson, Nicholas J.
ef38d847-22ec-4030-99cb-e77986b0815d
Ang, Wei
fab41904-013a-41f3-af55-3081a2383a85
Thiering, Elisabeth
15356ccf-7f02-4fc1-9a35-495029974930
Byrne, Enda M.
3b83950e-5aa8-4413-8f9e-7103d3819702
Taal, H. Rob
8272c1bf-c974-468e-9d80-fb8bf8a6b8d6
Huikari, Ville
2a8cd30c-dc8f-4655-a12d-b1db9318da7b
Bradfield, Jonathan P.
c61bfa2e-62eb-4dc0-965c-5ce529f9b5d1
Kerkhof, Marjan
9cac1b00-4b26-46d6-a3b2-0e7ea25836ad
Groen-Blokhuis, Maria M.
b84fb670-84dd-40ed-989f-1f3a2bcf57e2
Kreiner-Møller, Eskil
f5dee93b-b9d3-441c-92b8-b67a7a18d59d
Marinelli, Marcella
950edd7f-a3c4-4468-bed6-cb3d41f8f54c
Holst, Claus
011393f8-fb42-406b-bd2a-23ba66274dce
Leinonen, Jaakko T.
bfd1c628-9152-438a-afaf-81c133bdc6f2
Perry, John R. B.
e5f5491e-f421-4b29-99e6-195667572a31
Surakka, Ida
99141cb0-65ed-44eb-9ac0-ee5e30cc57bc
Pietiläinen, Olli
133b89a5-8f0b-4358-b3f0-00e477135774
Kettunen, Johannes
b62dfefc-9a70-40c0-90c2-df8ffb28bd4a
Anttila, Verneri
7216bfce-0eb9-479c-b27c-a014df2d0eb0
Kaakinen, Marika
25c15795-fcf9-43df-ad64-e29cb9107985
Sovio, Ulla
e7cd7dd6-dd07-498f-bba4-08cc12962698
Pouta, Anneli
108c5aa1-3b41-4095-91fa-ecd523934370
Das, Shikta
6ffdd16e-71b1-4bef-96b0-5c517b42227c
Lagou, Vasiliki
1ee28cf3-70ba-4b4c-b134-ea4622ff48c1
Power, Chris
21b17ff2-fabc-4782-9081-ab114c99a3a4
Prokopenko, Inga
e56ceffd-52b1-4503-ac82-adc537595e6e
Evans, David M.
7adf29d1-837e-4c60-8e1c-247dc8e3b68b
Kemp, John P.
e55b0aa0-e9b7-4c08-b43e-7e8fc4132baf
St Pourcain, Beate
ee25cc32-350b-4b07-8212-ae7db001b95e
Ring, Susan
79941daa-7ae8-47f1-beb4-e8560ce12fd8
Palotie, Aarno
c6fe081c-2fd2-4317-bb0a-928dd6b36f68
Kajantie, Eero
d68d55b6-6df1-4195-a914-44c738a6db93
Osmond, Clive
2677bf85-494f-4a78-adf8-580e1b8acb81
Lehtimäki, Terho
c8c72e98-8043-42dc-99d2-7574ff4c3d6b
Viikari, Jorma S.
68bb39bb-54e2-437f-9bee-48a6682de962
Kähönen, Mika
1155e797-98f0-4204-96be-b8f410155340
Warrington, Nicole M.
d02e0311-3a40-43fc-9a01-41e3e44043f5
Lye, Stephen J.
ff9be6e2-3953-4c07-8607-c5b8bf6b6742
Palmer, Lyle J.
089fb1c1-12e1-4ece-9bfa-7b404cee4772
Tiesler, Carla M. T.
b9616ef2-584f-4c0d-888f-e712c729e123
Flexeder, Claudia
5c750c40-7c85-449b-a0af-7a33475bece3
Montgomery, Grant W.
3985a36e-268f-4e2a-bbb5-483df9cbd46e
Medland, Sarah E.
c1db8cd0-d80d-40d2-8daf-40a2589f28cd
Hofman, Albert
19e6a48f-bef9-43bd-8c54-1b6057ead0bc
Hakonarson, Hakon
2bbcbada-c11d-41b6-acbe-32e998c8f6c3
Guxens, Mònica
b1697eaf-1b6c-4e3d-9124-9b728e08a742
Bartels, Meike
e9050398-295b-48c2-94aa-ee54e063ffc9
Salomaa, Veikko
1cbf3c25-5c3b-49a4-9f8c-83f2fd475d49
Murabito, Joanne M.
bb0e2310-60fb-4fce-a665-67d5d1cec2ce
Kaprio, Jaakko
de018b67-5b73-4c34-94af-8fbc4a4ff34d
Sørensen, Thorkild I. A.
c2e37ca6-5a48-4728-b64c-fc998cc60906
Ballester, Ferran
38a13673-0a6d-4f9f-a732-3a6040f66be2
Bisgaard, Hans
9c218eab-ee81-4fbf-97db-c0352a694491
Boomsma, Dorret I.
927599c7-a52e-4c3e-9179-12b09d916801
Koppelman, Gerard H.
8d04aab8-5795-4e62-b64a-de7e368c0d1d
Grant, Struan F. A.
2ff73b7e-e3e0-49e6-8cc0-c55aca29eeb4
Jaddoe, Vincent W. V.
839dd407-127e-49dc-aeba-bdc78be1eccb
Martin, Nicholas G.
fe228d93-a4d7-45b8-9c7b-1e0328fcb011
Heinrich, Joachim
bd0a5948-41cb-4541-87ad-1b86e51f6d2a
Pennell, Craig E.
6e6df3ca-42b8-4610-bc13-a3e38d0b6c7f
Raitakari, Olli T.
6cf56ed9-a97a-45b6-8722-0aacc3e85f73
Eriksson, Johan G.
eb96b1c5-af07-4a52-8a73-7541451d32cd
Smith, George Davey
f5bc8327-f2cb-49a0-8eae-4a6ba63207a2
Hyppönen, Elina
b5cfde7c-5b61-4034-ab80-c5eaa9eeeb3d
Järvelin, Marjo-Riitta
eb1fa1c9-add7-4f22-b314-1548d28a286b
McCarthy, Mark I.
ff42236d-bc18-406f-898b-d10ce8d0bab2
Ripatti, Samuli
705fa391-c779-4941-814c-8ce1f8fbefb7
Widén, Elisabeth
6ab65fda-5375-417c-9711-35452c49f709
Cousminer, Diana L.
f35f6690-1236-4392-9c4c-867cc437c832
Berry, Diane J.
a624d6c2-49a2-4162-bab2-ed1641c61c51
Timpson, Nicholas J.
ef38d847-22ec-4030-99cb-e77986b0815d
Ang, Wei
fab41904-013a-41f3-af55-3081a2383a85
Thiering, Elisabeth
15356ccf-7f02-4fc1-9a35-495029974930
Byrne, Enda M.
3b83950e-5aa8-4413-8f9e-7103d3819702
Taal, H. Rob
8272c1bf-c974-468e-9d80-fb8bf8a6b8d6
Huikari, Ville
2a8cd30c-dc8f-4655-a12d-b1db9318da7b
Bradfield, Jonathan P.
c61bfa2e-62eb-4dc0-965c-5ce529f9b5d1
Kerkhof, Marjan
9cac1b00-4b26-46d6-a3b2-0e7ea25836ad
Groen-Blokhuis, Maria M.
b84fb670-84dd-40ed-989f-1f3a2bcf57e2
Kreiner-Møller, Eskil
f5dee93b-b9d3-441c-92b8-b67a7a18d59d
Marinelli, Marcella
950edd7f-a3c4-4468-bed6-cb3d41f8f54c
Holst, Claus
011393f8-fb42-406b-bd2a-23ba66274dce
Leinonen, Jaakko T.
bfd1c628-9152-438a-afaf-81c133bdc6f2
Perry, John R. B.
e5f5491e-f421-4b29-99e6-195667572a31
Surakka, Ida
99141cb0-65ed-44eb-9ac0-ee5e30cc57bc
Pietiläinen, Olli
133b89a5-8f0b-4358-b3f0-00e477135774
Kettunen, Johannes
b62dfefc-9a70-40c0-90c2-df8ffb28bd4a
Anttila, Verneri
7216bfce-0eb9-479c-b27c-a014df2d0eb0
Kaakinen, Marika
25c15795-fcf9-43df-ad64-e29cb9107985
Sovio, Ulla
e7cd7dd6-dd07-498f-bba4-08cc12962698
Pouta, Anneli
108c5aa1-3b41-4095-91fa-ecd523934370
Das, Shikta
6ffdd16e-71b1-4bef-96b0-5c517b42227c
Lagou, Vasiliki
1ee28cf3-70ba-4b4c-b134-ea4622ff48c1
Power, Chris
21b17ff2-fabc-4782-9081-ab114c99a3a4
Prokopenko, Inga
e56ceffd-52b1-4503-ac82-adc537595e6e
Evans, David M.
7adf29d1-837e-4c60-8e1c-247dc8e3b68b
Kemp, John P.
e55b0aa0-e9b7-4c08-b43e-7e8fc4132baf
St Pourcain, Beate
ee25cc32-350b-4b07-8212-ae7db001b95e
Ring, Susan
79941daa-7ae8-47f1-beb4-e8560ce12fd8
Palotie, Aarno
c6fe081c-2fd2-4317-bb0a-928dd6b36f68
Kajantie, Eero
d68d55b6-6df1-4195-a914-44c738a6db93
Osmond, Clive
2677bf85-494f-4a78-adf8-580e1b8acb81
Lehtimäki, Terho
c8c72e98-8043-42dc-99d2-7574ff4c3d6b
Viikari, Jorma S.
68bb39bb-54e2-437f-9bee-48a6682de962
Kähönen, Mika
1155e797-98f0-4204-96be-b8f410155340
Warrington, Nicole M.
d02e0311-3a40-43fc-9a01-41e3e44043f5
Lye, Stephen J.
ff9be6e2-3953-4c07-8607-c5b8bf6b6742
Palmer, Lyle J.
089fb1c1-12e1-4ece-9bfa-7b404cee4772
Tiesler, Carla M. T.
b9616ef2-584f-4c0d-888f-e712c729e123
Flexeder, Claudia
5c750c40-7c85-449b-a0af-7a33475bece3
Montgomery, Grant W.
3985a36e-268f-4e2a-bbb5-483df9cbd46e
Medland, Sarah E.
c1db8cd0-d80d-40d2-8daf-40a2589f28cd
Hofman, Albert
19e6a48f-bef9-43bd-8c54-1b6057ead0bc
Hakonarson, Hakon
2bbcbada-c11d-41b6-acbe-32e998c8f6c3
Guxens, Mònica
b1697eaf-1b6c-4e3d-9124-9b728e08a742
Bartels, Meike
e9050398-295b-48c2-94aa-ee54e063ffc9
Salomaa, Veikko
1cbf3c25-5c3b-49a4-9f8c-83f2fd475d49
Murabito, Joanne M.
bb0e2310-60fb-4fce-a665-67d5d1cec2ce
Kaprio, Jaakko
de018b67-5b73-4c34-94af-8fbc4a4ff34d
Sørensen, Thorkild I. A.
c2e37ca6-5a48-4728-b64c-fc998cc60906
Ballester, Ferran
38a13673-0a6d-4f9f-a732-3a6040f66be2
Bisgaard, Hans
9c218eab-ee81-4fbf-97db-c0352a694491
Boomsma, Dorret I.
927599c7-a52e-4c3e-9179-12b09d916801
Koppelman, Gerard H.
8d04aab8-5795-4e62-b64a-de7e368c0d1d
Grant, Struan F. A.
2ff73b7e-e3e0-49e6-8cc0-c55aca29eeb4
Jaddoe, Vincent W. V.
839dd407-127e-49dc-aeba-bdc78be1eccb
Martin, Nicholas G.
fe228d93-a4d7-45b8-9c7b-1e0328fcb011
Heinrich, Joachim
bd0a5948-41cb-4541-87ad-1b86e51f6d2a
Pennell, Craig E.
6e6df3ca-42b8-4610-bc13-a3e38d0b6c7f
Raitakari, Olli T.
6cf56ed9-a97a-45b6-8722-0aacc3e85f73
Eriksson, Johan G.
eb96b1c5-af07-4a52-8a73-7541451d32cd
Smith, George Davey
f5bc8327-f2cb-49a0-8eae-4a6ba63207a2
Hyppönen, Elina
b5cfde7c-5b61-4034-ab80-c5eaa9eeeb3d
Järvelin, Marjo-Riitta
eb1fa1c9-add7-4f22-b314-1548d28a286b
McCarthy, Mark I.
ff42236d-bc18-406f-898b-d10ce8d0bab2
Ripatti, Samuli
705fa391-c779-4941-814c-8ce1f8fbefb7
Widén, Elisabeth
6ab65fda-5375-417c-9711-35452c49f709

Cousminer, Diana L., Berry, Diane J., Timpson, Nicholas J., Ang, Wei, Thiering, Elisabeth, Byrne, Enda M., Taal, H. Rob, Huikari, Ville, Bradfield, Jonathan P., Kerkhof, Marjan, Groen-Blokhuis, Maria M., Kreiner-Møller, Eskil, Marinelli, Marcella, Holst, Claus, Leinonen, Jaakko T., Perry, John R. B., Surakka, Ida, Pietiläinen, Olli, Kettunen, Johannes, Anttila, Verneri, Kaakinen, Marika, Sovio, Ulla, Pouta, Anneli, Das, Shikta, Lagou, Vasiliki, Power, Chris, Prokopenko, Inga, Evans, David M., Kemp, John P., St Pourcain, Beate, Ring, Susan, Palotie, Aarno, Kajantie, Eero, Osmond, Clive, Lehtimäki, Terho, Viikari, Jorma S., Kähönen, Mika, Warrington, Nicole M., Lye, Stephen J., Palmer, Lyle J., Tiesler, Carla M. T., Flexeder, Claudia, Montgomery, Grant W., Medland, Sarah E., Hofman, Albert, Hakonarson, Hakon, Guxens, Mònica, Bartels, Meike, Salomaa, Veikko, Murabito, Joanne M., Kaprio, Jaakko, Sørensen, Thorkild I. A., Ballester, Ferran, Bisgaard, Hans, Boomsma, Dorret I., Koppelman, Gerard H., Grant, Struan F. A., Jaddoe, Vincent W. V., Martin, Nicholas G., Heinrich, Joachim, Pennell, Craig E., Raitakari, Olli T., Eriksson, Johan G., Smith, George Davey, Hyppönen, Elina, Järvelin, Marjo-Riitta, McCarthy, Mark I., Ripatti, Samuli and Widén, Elisabeth (2013) Genome-wide association and longitudinal analyses reveal genetic loci linking pubertal height growth, pubertal timing and childhood adiposity. Human Molecular Genetics, 22 (13), 2735-2747. (doi:10.1093/hmg/ddt104). (PMID:23449627)

Record type: Article

Abstract

The pubertal height growth spurt is a distinctive feature of childhood growth reflecting both the central onset of puberty and local growth factors. Although little is known about the underlying genetics, growth variability during puberty correlates with adult risks for hormone-dependent cancer and adverse cardiometabolic health. The only gene so far associated with pubertal height growth, LIN28B, pleiotropically influences childhood growth, puberty and cancer progression, pointing to shared underlying mechanisms. To discover genetic loci influencing pubertal height and growth and to place them in context of overall growth and maturation, we performed genome-wide association meta-analyses in 18 737 European samples utilizing longitudinally collected height measurements. We found significant associations (P < 1.67 × 10(-8)) at 10 loci, including LIN28B. Five loci associated with pubertal timing, all impacting multiple aspects of growth. In particular, a novel variant correlated with expression of MAPK3, and associated both with increased prepubertal growth and earlier menarche. Another variant near ADCY3-POMC associated with increased body mass index, reduced pubertal growth and earlier puberty. Whereas epidemiological correlations suggest that early puberty marks a pathway from rapid prepubertal growth to reduced final height and adult obesity, our study shows that individual loci associating with pubertal growth have variable longitudinal growth patterns that may differ from epidemiological observations. Overall, this study uncovers part of the complex genetic architecture linking pubertal height growth, the timing of puberty and childhood obesity and provides new information to pinpoint processes linking these traits.

Text
Cousminer Genome-wide association.pdf - Other
Restricted to Repository staff only
Request a copy

More information

e-pub ahead of print date: 27 February 2013
Published date: 1 July 2013
Organisations: Human Development & Health

Identifiers

Local EPrints ID: 355131
URI: http://eprints.soton.ac.uk/id/eprint/355131
PURE UUID: ea8eed7a-ee06-43e8-a14a-4bd2dd6d340b
ORCID for Clive Osmond: ORCID iD orcid.org/0000-0002-9054-4655

Catalogue record

Date deposited: 09 Aug 2013 09:14
Last modified: 15 Mar 2024 02:50

Export record

Altmetrics

Contributors

Author: Diana L. Cousminer
Author: Diane J. Berry
Author: Nicholas J. Timpson
Author: Wei Ang
Author: Elisabeth Thiering
Author: Enda M. Byrne
Author: H. Rob Taal
Author: Ville Huikari
Author: Jonathan P. Bradfield
Author: Marjan Kerkhof
Author: Maria M. Groen-Blokhuis
Author: Eskil Kreiner-Møller
Author: Marcella Marinelli
Author: Claus Holst
Author: Jaakko T. Leinonen
Author: John R. B. Perry
Author: Ida Surakka
Author: Olli Pietiläinen
Author: Johannes Kettunen
Author: Verneri Anttila
Author: Marika Kaakinen
Author: Ulla Sovio
Author: Anneli Pouta
Author: Shikta Das
Author: Vasiliki Lagou
Author: Chris Power
Author: Inga Prokopenko
Author: David M. Evans
Author: John P. Kemp
Author: Beate St Pourcain
Author: Susan Ring
Author: Aarno Palotie
Author: Eero Kajantie
Author: Clive Osmond ORCID iD
Author: Terho Lehtimäki
Author: Jorma S. Viikari
Author: Mika Kähönen
Author: Nicole M. Warrington
Author: Stephen J. Lye
Author: Lyle J. Palmer
Author: Carla M. T. Tiesler
Author: Claudia Flexeder
Author: Grant W. Montgomery
Author: Sarah E. Medland
Author: Albert Hofman
Author: Hakon Hakonarson
Author: Mònica Guxens
Author: Meike Bartels
Author: Veikko Salomaa
Author: Joanne M. Murabito
Author: Jaakko Kaprio
Author: Thorkild I. A. Sørensen
Author: Ferran Ballester
Author: Hans Bisgaard
Author: Dorret I. Boomsma
Author: Gerard H. Koppelman
Author: Struan F. A. Grant
Author: Vincent W. V. Jaddoe
Author: Nicholas G. Martin
Author: Joachim Heinrich
Author: Craig E. Pennell
Author: Olli T. Raitakari
Author: Johan G. Eriksson
Author: George Davey Smith
Author: Elina Hyppönen
Author: Marjo-Riitta Järvelin
Author: Mark I. McCarthy
Author: Samuli Ripatti
Author: Elisabeth Widén

Download statistics

Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.

View more statistics

Atom RSS 1.0 RSS 2.0

Contact ePrints Soton: eprints@soton.ac.uk

ePrints Soton supports OAI 2.0 with a base URL of http://eprints.soton.ac.uk/cgi/oai2

This repository has been built using EPrints software, developed at the University of Southampton, but available to everyone to use.

We use cookies to ensure that we give you the best experience on our website. If you continue without changing your settings, we will assume that you are happy to receive cookies on the University of Southampton website.

×